Turning astrocytes from the rostral migratory stream into neurons: a role for the olfactory sensory organ.
Neurogenesis persists within a few restricted areas of the adult mammalian brain, giving rise to neurons that functionally integrate into preexisting circuits. One of these areas, the subventricular zone (SVZ), was believed, until recently, to be the unique source providing the adult olfactory bulb (OB) with newborn neurons. Because of the fact that neuroblasts derived in the SVZ migrate through the rostral migratory stream (RMS) en route to the OB, the existence of candidate neural stem cells within the RMS was long overlooked. Here, we confirm and considerably extend recent evidence for the existence of adult neural stem cells within the RMS, and go on to investigate their proliferative regulation. Specifically targeting RMS-astrocytes with lentiviral vectors encoding GFP, we demonstrate that glial cells in the RMS differentiate into both OB granule and periglomerular interneurons. In addition, ultrastructural analysis unambiguously reveals the astrocytic nature of stem cells in the adult RMS, and patch-clamp recordings demonstrate the functional integration of RMS-derived interneurons into OB circuitry. Proliferative regulation was investigated via two contrasting manipulations: exposure to an odor-enriched environment that enhances candidate stem cell proliferation in both the RMS and SVZ, and chemical lesion of the main olfactory epithelium that increases cell proliferation in the RMS only. New neurons in the adult OB can therefore arise from different neurogenic areas that can be separately regulated.
Alonso
Mariana
M
Laboratory for Perception and Memory, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2182, Institut Pasteur, 75724 Paris Cedex 15, France.
Ortega-Pérez
Inmaculada
I
Grubb
Matthew S
MS
Bourgeois
Jean-Pierre
JP
Charneau
Pierre
P
Lledo
Pierre-Marie
PM
D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000166:cytology; D005822:Genetic Vectors / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D016086:Lentivirus / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009812:Odorants; D009831:Olfactory Mucosa / Q000166:cytology* / Q000293:injuries / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D013268:Stimulation, Chemical; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001973:Bromodeoxyuridine